Loganin prevents BV-2 microglia cells from Aβ_1-42 -induced inflammation via regulating TLR4/TRAF6/NF-κB axis

Neuroinflammation is closely related with the pathogenesis and progress of neurodegenerative diseases including Alzheimer's disease (AD). Loganin, an iridoid glycoside obtained from traditional Chinese medicine Cornus officinalis, has properties of inhibiting inflammation and improving memory. The present study was aimed to investigate effects of loganin on Aβ-induced inflammation and to explore the underlying mechanisms. BV-2 microglia cells were stimulated with 10 µM Aβ_1-42 for 24 h to induce inflammatory damage. According to results of CCK-8 assay, the doses of loganin in present work were 10 and 30 µM. We found that treatment with loganin could inhibit Aβ_1-42 -induced microglia activation. Furthermore, loganin treatment prevented the over-production of Tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), Macrophage Chemotactic Protein 1(MCP-1), Nitric oxide (NO), Prostaglandin E2 (PGE2) and the up-regulation of inducible nitric oxide synthase (iNOS) and Cyclooxygenase 2 (COX-2) in Aβ_1-42 -stimulated BV-2 cells. Results from Western blots demonstrated that loganin inhibited Aβ_1-42 -induced elevation in Toll-like receptor 4 (TLR4), Myeloid Differentiation Factor 88 (MyD88) and TNF receptor-associated factor 6 (TRAF6). Loganin treatment also attenuated the increased phosphorylation level of IRAK4 caused by Aβ_1-42 . Additionally, loganin alleviated nuclear translocation of NF-κB p65 subunit in Aβ_1-42 -stimulated BV-2 cells, and this phenomenon could be reversed by TLR4 agonist LPS. Further, the anti-inflammatory effects of loganin were attenuated when TLR4 signaling pathway was re-activated by LPS. Taken together, our data indicated that loganin could attenuate inflammatory response induced by Aβ in BV-2 microglia cells, partially through deactivating the TLR4/TRAF6/NF-κB axis.